Project Summary Obsessive compulsive disorder (OCD) affects 2-3% of the population and is characterized by obsessional, obtrusive thoughts and compulsive behaviors, that interfere with interpersonal and occupational function, sometimes to a severe extent. Given the critical need for biomarkers of OCD to inform underlying neurobiological processes and provide targets for treatment choices, one way forward to meet this need is to identify in individuals with OCD specific functional and structural abnormalities in neural networks putatively associated with the illness. Our overarching hypothesis is that there is a neural network that is dysfunctional in OCD, and that this may be associated with development of the excessive ritualized behaviors that characterize the illness. This neural network includes dorsal anterior cingulate cortex, orbitofrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, ventromedial prefrontal cortex, amygdala and dorsal striatum. The overarching goal of Project 2 (P2) in this proposed center is thus to identify key resting state functional connectivity abnormalities, and abnormalities in underlying white matter, in this circuitry in adults with OCD. We will use fMRI to examine resting state connectivity among these regions, and diffusion imaging and probabilistic tractography to examine white matter in tracts connecting these regions in individuals with OCD. We will use state of the art shimming routines to optimize the signal: noise ratio in regions in this neural network. P2 thereby aims to examine in 40 unmedicated/SRI/clomipramine medicated adults with OCD versus 40 healthy adults (aged 18-35 years): 1. Resting state connectivity, to provide a measure of ?tonic? functional connectivity among these regions. 2. White matter connectivity among these regions. 3. We will also determine relationships between these measures of resting state connectivity and white matter in the neural network to better understand the integration between structural and functional connections in this network. P2, together with other projects in the center, will inform understanding of functional and white matter connection abnormalities in the above neural network in OCD, and will provide neurobiological measures to ultimately inform treatment choice and novel treatments for the illness.